This invention relates to a process for resolving (.+-.)-1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid using cholesteryl aniline to obtain the corresponding (+)-enantiomer.
(.+-.)-1,8-Diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid, an optically inactive racemic mixture, is known generically as etodolic acid or etodolac and is well known as an anti-inflammatory and analgesic agent, C. A. Demerson et al., U.S. Pat. No. 3,939,178, issued Feb. 17, 1976; and C. A. Demerson et al., J. Med. Chem., 18, 189 (1975) and 19, 391 (1976).
The resolution of racemic organic acids is unpredictable. Attempts to resolve etodolac have been plagued with numerous problems, for example, crystallization of the wrong enanthiomer, selection of an appropriate base for forming the diastereoisomeric salt, low yields, multiple crystallizations and time consumption.
The herein described process avoids the above problems and the (.+-.)-enantiomer is obtained in high yield and in a commercially feasible operation.